TRPV1 and TRPA1 Channels Are Both Involved Downstream of Histamine-Induced Itch

Biomolecules. 2021 Aug 6;11(8):1166. doi: 10.3390/biom11081166.

Abstract

Two histamine receptor subtypes (HR), namely H1R and H4R, are involved in the transmission of histamine-induced itch as key components. Although exact downstream signaling mechanisms are still elusive, transient receptor potential (TRP) ion channels play important roles in the sensation of histaminergic and non-histaminergic itch. The aim of this study was to investigate the involvement of TRPV1 and TRPA1 channels in the transmission of histaminergic itch. The potential of TRPV1 and TRPA1 inhibitors to modulate H1R- and H4R-induced signal transmission was tested in a scratching assay in mice in vivo as well as via Ca2+ imaging of murine sensory dorsal root ganglia (DRG) neurons in vitro. TRPV1 inhibition led to a reduction of H1R- and H4R- induced itch, whereas TRPA1 inhibition reduced H4R- but not H1R-induced itch. TRPV1 and TRPA1 inhibition resulted in a reduced Ca2+ influx into sensory neurons in vitro. In conclusion, these results indicate that both channels, TRPV1 and TRPA1, are involved in the transmission of histamine-induced pruritus.

Keywords: Ca2+-imaging; TRPA1; TRPV1; dorsal root ganglion neurons (DRG); histamine; histamine H1 receptor; histamine H4 receptor; itch; signal transduction.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetanilides / pharmacology
  • Animals
  • Calcium / metabolism*
  • Capsaicin / analogs & derivatives
  • Capsaicin / pharmacology
  • Female
  • Ganglia, Spinal / drug effects
  • Ganglia, Spinal / metabolism*
  • Gene Expression
  • Histamine / administration & dosage
  • Male
  • Methylhistamines / administration & dosage
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Molecular Imaging
  • Primary Cell Culture
  • Pruritus / chemically induced
  • Pruritus / drug therapy
  • Pruritus / genetics*
  • Pruritus / metabolism
  • Purines / pharmacology
  • Ruthenium Red / pharmacology
  • Sensory Receptor Cells / drug effects
  • Sensory Receptor Cells / metabolism*
  • Signal Transduction
  • TRPA1 Cation Channel / antagonists & inhibitors
  • TRPA1 Cation Channel / genetics*
  • TRPA1 Cation Channel / metabolism
  • TRPV Cation Channels / antagonists & inhibitors
  • TRPV Cation Channels / genetics*
  • TRPV Cation Channels / metabolism

Substances

  • 2-(1,3-dimethyl-2,6-dioxo-1,2,3,6-tetrahydro-7H-purin-7-yl)-N-(4-isopropylphenyl)acetamide
  • Acetanilides
  • Methylhistamines
  • Purines
  • TRPA1 Cation Channel
  • TRPV Cation Channels
  • TRPV1 protein, mouse
  • Trpa1 protein, mouse
  • Ruthenium Red
  • 4-methylhistamine
  • Histamine
  • capsazepine
  • Capsaicin
  • Calcium